Document Detail

Periostin induces proliferation of human autosomal dominant polycystic kidney cells through alphaV-integrin receptor.
MedLine Citation:
PMID:  18753297     Owner:  NLM     Status:  MEDLINE    
Progressive renal enlargement due to the growth of innumerable fluid-filled cysts is a central pathophysiological feature of autosomal dominant polycystic kidney disease (ADPKD). These epithelial neoplasms enlarge slowly and damage noncystic parenchyma by mechanisms that have not been clearly defined. In a microarray analysis of cultured human ADPKD cyst epithelial cells, periostin mRNA was overexpressed 15-fold compared with normal human kidney (NHK) cells. Periostin, initially identified in osteoblasts, is not expressed in normal adult kidneys but is expressed transiently during renal development. We found periostin in cyst-lining cells in situ in the extracellular matrix adjacent to the cysts and within cyst fluid. ADPKD cells secreted periostin across luminal and basolateral plasma membranes. Periostin increased proliferation of cyst epithelial cells 27.9 +/- 3.1% (P < 0.001) above baseline and augmented in vitro cyst growth but did not affect proliferation of normal renal cells. Expression of alphaV-integrin, a periostin receptor, was ninefold higher in ADPKD cells compared with NHK cells, and antibodies that block alphaV-integrin inhibited periostin-induced cell proliferation. We conclude that periostin is a novel autocrine mitogen secreted by mural epithelial cells with the potential to accelerate cyst growth and promote interstitial remodeling in ADPKD.
Darren P Wallace; Megan T Quante; Gail A Reif; Emily Nivens; Farhana Ahmed; Scott J Hempson; Gustavo Blanco; Tamio Yamaguchi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-08-27
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  295     ISSN:  1931-857X     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-06     Completed Date:  2009-02-09     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F1463-71     Citation Subset:  IM    
Kidney Institute, Department of Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, MSN 3018, Kansas City, Kansas 66160, USA.
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MeSH Terms
Antibodies / immunology,  pharmacology
Cell Adhesion Molecules / genetics,  pharmacology,  physiology*
Cell Cycle / drug effects
Cell Proliferation*
Cells, Cultured
Cyclic AMP / pharmacology
Cyst Fluid / metabolism
Cysts / metabolism,  pathology
Epidermal Growth Factor / pharmacology
Epithelial Cells / cytology,  drug effects,  metabolism
Extracellular Matrix / metabolism
Flow Cytometry
Forskolin / pharmacology
Gene Expression / drug effects
Integrin alphaV / genetics,  immunology,  physiology*
Kidney / metabolism,  pathology
Polycystic Kidney, Autosomal Dominant / genetics,  metabolism,  pathology
Recombinant Proteins / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Transforming Growth Factor beta / genetics,  pharmacology
Grant Support
Reg. No./Substance:
0/Antibodies; 0/Cell Adhesion Molecules; 0/Integrin alphaV; 0/POSTN protein, human; 0/Recombinant Proteins; 0/Transforming Growth Factor beta; 60-92-4/Cyclic AMP; 62229-50-9/Epidermal Growth Factor; 66428-89-5/Forskolin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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